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miR-20b is up-regulated in brain metastases from primary breast cancers.

Ahmad A, Ginnebaugh KR, Sethi S, Chen W, Ali R, Mittal S, Sarkar FH - Oncotarget (2015)

Bottom Line: However, unique molecular biomarkers have not yet been established.We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells.Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.

ABSTRACT
Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.

No MeSH data available.


Related in: MedlinePlus

Relative expression of miR-20b in brain vs. bone-seeking breast cancer cellsExpression of miR-20b was determined by quantitative RT-PCR. RNU48 was used as internal miRNA control against which the data was normalized. BR, Brain-metastasizing MDA-MB-231 cells; BO, Bone-metastasizing MDA-MB-231 cells. *p < 0.01.
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Figure 5: Relative expression of miR-20b in brain vs. bone-seeking breast cancer cellsExpression of miR-20b was determined by quantitative RT-PCR. RNU48 was used as internal miRNA control against which the data was normalized. BR, Brain-metastasizing MDA-MB-231 cells; BO, Bone-metastasizing MDA-MB-231 cells. *p < 0.01.

Mentions: The results from patient-derived samples suggested an involvement of miR-20b in brain metastasis of breast cancer. In order to test whether expression of miR-20b is a specific predictor of brain metastasis, we checked its expression in brain vs. bone-seeking derivatives of MDA-MB-231 cells. These brain- and bone-seeking cells were established by repeated sequential passages in nude mice and in vitro of metastatic cells obtained from brain and bone metastases, respectively [18]. When analyzed for endogenous miR-20b levels, we observed greater than 2.5-fold increased levels of miR-20b in brain-seeking cells, compared to bone seeking cells (p < 0.01) (Figure 5). Significantly higher expression of miR-20b in brain-seeking cells is indicative of the role of miR-20b in brain-specific metastasis of breast cancer cells. These results suggest that miR-20b might be a specific biomarker for breast cancers with high propensity to metastasize to brain.


miR-20b is up-regulated in brain metastases from primary breast cancers.

Ahmad A, Ginnebaugh KR, Sethi S, Chen W, Ali R, Mittal S, Sarkar FH - Oncotarget (2015)

Relative expression of miR-20b in brain vs. bone-seeking breast cancer cellsExpression of miR-20b was determined by quantitative RT-PCR. RNU48 was used as internal miRNA control against which the data was normalized. BR, Brain-metastasizing MDA-MB-231 cells; BO, Bone-metastasizing MDA-MB-231 cells. *p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494931&req=5

Figure 5: Relative expression of miR-20b in brain vs. bone-seeking breast cancer cellsExpression of miR-20b was determined by quantitative RT-PCR. RNU48 was used as internal miRNA control against which the data was normalized. BR, Brain-metastasizing MDA-MB-231 cells; BO, Bone-metastasizing MDA-MB-231 cells. *p < 0.01.
Mentions: The results from patient-derived samples suggested an involvement of miR-20b in brain metastasis of breast cancer. In order to test whether expression of miR-20b is a specific predictor of brain metastasis, we checked its expression in brain vs. bone-seeking derivatives of MDA-MB-231 cells. These brain- and bone-seeking cells were established by repeated sequential passages in nude mice and in vitro of metastatic cells obtained from brain and bone metastases, respectively [18]. When analyzed for endogenous miR-20b levels, we observed greater than 2.5-fold increased levels of miR-20b in brain-seeking cells, compared to bone seeking cells (p < 0.01) (Figure 5). Significantly higher expression of miR-20b in brain-seeking cells is indicative of the role of miR-20b in brain-specific metastasis of breast cancer cells. These results suggest that miR-20b might be a specific biomarker for breast cancers with high propensity to metastasize to brain.

Bottom Line: However, unique molecular biomarkers have not yet been established.We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells.Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.

ABSTRACT
Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.

No MeSH data available.


Related in: MedlinePlus